Mechanics of Neural tube Formation

Brain and spinal cord development begin with the folding of the embryonic neural tissue into a tube. Many of the molecular and cellular processes which drive neural tube folding have been elucidated in animal models. However, understanding how such noisy microscopic activities collectively integrate to drive coherent shape changes at the tissue scale remains a challenge. To address this question, we developed a human stem-cell system that self-organizes into a neural tube in a dish. Our system offers quantitative control over experimental parameters including tissue geometry, mechanical environment, and morphogen gradients - all of which are challenging to control in a living embryo. Through a combination of quantitative imaging and genetic perturbations, we plan to advance our understanding of human neural tube formation in health and disease.

Human Birth Defects

Failures in neural tube folding are among the most common birth defects, affecting 1:1000 pregnancies. Neural tube defects result in severe disabilities and lethality shortly after birth. Surprisingly, there are multiple genetic mutations associated with neural tube defects in humans that do not lead to defects in mice. Our stem-cell platform offers a unique opportunity to study how neural tube morphogenesis is regulated by the human genome and to understand its evolution across species. 

Synthetic Morphogenesis

Organ shape information is encoded in genetic networks and in the boundary and initial conditions of the tissue. Our 3D stem-cell sheets are a clean slate on which we can quantitatively explore this idea. We will study how tissue geometry, mechanical environment, and positioning of morphogens control tissue morphogenesis. We aim to understand how organ shapes are determined during embryonic development and to design new synthetic forms.